Patients with well-documented post-transfusion chronic non-A, non-B hepatitis are being evaluated to determine the long-term natural history of this disease and to obtain tissue and reagents to search for non-A, non-B specific agents. Thirty patients have been admitted to this study. Follow-up of these patients for periods ranging from 1-12 years has demonstrated that, while this disease is usually insidious and asymptomatic, up to 20% (6/30) of patients ultimately develop cirrhosis. One of the 30 patients has died from chronic liver failure and another is disabled from symptoms of chronic liver disease. Preliminary studies of alpha interferon therapy have been initiated in patients with chronic non-A, non-B hepatitis. Two patients have been treated with interferon, one for a year and one for four months. In both patients, therapy was associated with an appreciable fall in elevated levels of serum aminotranferases. The improved levels occurred after one month of therapy in one patient and after three months of therapy in the other. A follow-up liver biopsy in the patient treated for one year demonstrated a marked decrease in the chronic hepatitis disease activity. A pilot study of alpha interferon therapy in 5-10 further patients is planned.